Browsing by Subject "Organelles"

Now showing 1 - 4 of 4
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    ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points
    (JCB, 2022-02-17) Krey, Jocelyn F.; Liu, Chang; Belyantseva, Inna A.; Bateschell, Michael; Dumont, Rachel A.; Goldsmith, Jennifer; Chatterjee, Paroma; Morrill, Rachel S.; Fedorov, Lev M.; Foster, Sarah; Kim, Jinkyung; Nuttall, Alfred L.; Jones, Sherri M.; Choi, Dongseok; Friedman, Thomas B.; Ricci, Anthony J.; Zhao, Bo; Barr-Gillespie, Peter G.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell’s cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed–TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience.
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    Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism
    (Springer Nature, 2023) Han, Lei; Huang, Dayang; Wu, Shiyong; Liu, Sheng; Wang, Cheng; Sheng, Yi; Lu, Xiongbin; Broxmeyer, Hal E.; Wan, Jun; Yang, Lei; Pediatrics, School of Medicine
    Lipid droplets (LDs) are cellular organelles critical for lipid homeostasis, with intramyocyte LD accumulation implicated in metabolic disorder-associated heart diseases. Here we identify a human long non-coding RNA, Lipid-Droplet Transporter (LIPTER), essential for LD transport in human cardiomyocytes. LIPTER binds phosphatidic acid and phosphatidylinositol 4-phosphate on LD surface membranes and the MYH10 protein, connecting LDs to the MYH10-ACTIN cytoskeleton and facilitating LD transport. LIPTER and MYH10 deficiencies impair LD trafficking, mitochondrial function and survival of human induced pluripotent stem cell-derived cardiomyocytes. Conditional Myh10 deletion in mouse cardiomyocytes leads to LD accumulation, reduced fatty acid oxidation and compromised cardiac function. We identify NKX2.5 as the primary regulator of cardiomyocyte-specific LIPTER transcription. Notably, LIPTER transgenic expression mitigates cardiac lipotoxicity, preserves cardiac function and alleviates cardiomyopathies in high-fat-diet-fed and Leprdb/db mice. Our findings unveil a molecular connector role of LIPTER in intramyocyte LD transport, crucial for lipid metabolism of the human heart, and hold significant clinical implications for treating metabolic syndrome-associated heart diseases.
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    Protein control of membrane and organelle dynamics: Insights from the divergent eukaryote Toxoplasma gondii
    (Elsevier, 2022) Ovciarikova, Jana; Oliveira Souza, Rodolpho Ornitz; Arrizabalaga, Gustavo; Sheiner, Lilach; Pharmacology and Toxicology, School of Medicine
    Integral membrane protein complexes control key cellular functions in eukaryotes by defining membrane-bound spaces within organelles and mediating inter-organelles contacts. Despite the critical role of membrane complexes in cell biology, most of our knowledge is from a handful of model systems, primarily yeast and mammals, while a full functional and evolutionary understanding remains incomplete without the perspective from a broad range of divergent organisms. Apicomplexan parasites are single-cell eukaryotes whose survival depends on organelle compartmentalisation and communication. Studies of a model apicomplexan, Toxoplasma gondii, reveal unexpected divergence in the composition and function of complexes previously considered broadly conserved, such as the mitochondrial ATP synthase and the tethers mediating ER-mitochondria membrane contact sites. Thus, Toxoplasma joins the repertoire of divergent model eukaryotes whose research completes our understanding of fundamental cell biology.
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    Quinoline Derivative MC1626, a Putative GCN5 Histone Acetyltransferase (HAT) Inhibitor, Exhibits HAT-Independent Activity against Toxoplasma gondii
    (American Society for Microbiology, 2007) Smith, Aaron T.; Livingston, Meredith R.; Mai, Antonello; Filetici, Patrizia; Queener, Sherry F.; Sullivan, William J., Jr.; Pharmacology and Toxicology, School of Medicine
    We report that quinoline derivative MC1626, first described as an inhibitor of the histone acetyltransferase (HAT) GCN5, is active against the protozoan parasite Toxoplasma gondii in vitro. However, MC1626 does not inhibit Toxoplasma GCN5 HATs or reduce HAT-mediated activity; rather, this quinoline may target the plastid organelle called the apicoplast.